Toxicology Department, Faculty of Pharmacy, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania.
Luxembourg Institute of Science and Technology (LIST), Environmental Research and Innovation (ERIN) Department, Environmental Health Group, Esch-sur-Alzette, Luxembourg.
Arch Toxicol. 2020 May;94(5):1417-1441. doi: 10.1007/s00204-020-02721-6. Epub 2020 Apr 4.
Depressive disorders are amongst the greatest mental health challenges, with an increasing number of patients being diagnosed each year. Though it has not yet been fully elucidated, redox metabolism imbalances and oxidative stress seem to play a major role in the pathogenesis of depressive disorders. Selective serotonin reuptake inhibitors (SSRIs) are the most prescribed antidepressants, considered to have a better tolerability. However, several adverse effects have been reported and the mechanisms involved in their pharmacological activity are not entirely understood. SSRIs have been shown to influence the redox metabolism, which could be involved in their toxicity and pharmacological effects. A comparative analysis of published in vivo and in vitro data regarding the activity of SSRIs on the redox metabolism pathways has been performed in this paper, with an emphasis on mechanistical aspects. Furthermore, a comparison between oxidative stress biomarker levels reported by different studies was attempted. The reviewed data point towards both pro- and antioxidant effects of SSRIs, dependent on tissue/cell type and dose/concentration, suggest a redox modulating potential of these compounds. In hepatic and testicular tissue, the majority of reviewed studies reported pro-oxidant effects, with possible implications towards the hepatotoxicity and sexual dysfunction that were reported following SSRI treatment; while in brain, the most common findings were antioxidant effects that could partially explain their antidepressant activity. However, given the heterogeneity of the reviewed data, further research is needed to fully understand the impact of SSRIs on redox metabolism and its implications.
抑郁障碍是最严重的心理健康挑战之一，每年被诊断出的患者数量不断增加。尽管其发病机制尚未完全阐明，但氧化还原代谢失衡和氧化应激似乎在抑郁障碍的发病机制中起着重要作用。选择性 5-羟色胺再摄取抑制剂（SSRIs）是最常被开的抗抑郁药，被认为具有更好的耐受性。然而，已经报道了一些不良反应，并且其药理活性涉及的机制尚未完全理解。SSRIs 已被证明会影响氧化还原代谢，这可能与其毒性和药理作用有关。本文对 SSRI 对氧化还原代谢途径的体内和体外活性的已发表数据进行了比较分析，重点是其机制方面。此外，还尝试比较了不同研究报告的氧化应激生物标志物水平。综述的数据表明，SSRIs 具有促氧化剂和抗氧化剂的双重作用，具体取决于组织/细胞类型以及剂量/浓度，提示这些化合物具有调节氧化还原的潜力。在肝和睾丸组织中，大多数综述研究报告了促氧化剂的作用，这可能与 SSRI 治疗后报告的肝毒性和性功能障碍有关；而在大脑中，最常见的发现是抗氧化作用，这可以部分解释它们的抗抑郁活性。然而，鉴于综述数据的异质性，需要进一步研究以充分了解 SSRIs 对氧化还原代谢的影响及其意义。
